Lei Zhijin, Tian Dongping, Zhang Chong, Zhao Shukun, Su Min
Department of Pathology and Institute of Clinical Pathology, Shantou University Medical College, Shantou, Guangdong, People's Republic of China.
Forensic Identification Center of Shantou University, Shantou University Medical College, Shantou, Guangdong, People's Republic of China.
BMC Cancer. 2016 Jul 7;16:410. doi: 10.1186/s12885-016-2462-3.
Chaoshan region, a littoral area of Guangdong province in southern China, has a high incidence of esophageal squamous cell carcinoma (ESCC). At present, the prognosis of ESCC is still very poor, therefore, there is urgent need to seek valuable molecular biomarker for prognostic evaluation to guide clinical treatment. GPX2, a selenoprotein, was exclusively expressed in gastrointestinal tract and has an anti-oxidative damage and anti-tumour effect in the progress of tumourigenesis.
We collected 161 ESCC patients samples, among which 83 patients were followed up. We employed immunochemistry analysis, western blotting and quantitative real-time PCR for measuring the expression of GPX2 within ESCC samples. We analysed the relationship between the expression of GPX2 and clinicopathological parameters of 161 patients with ESCC by Chi-square or Fisher's exact test. The survival analysis of GPX2 expression within ESCC tissues was evaluated by the Kaplan-Meier method and Cox-regression.
A significant higher expression level of GPX2 was detected in tumour tissues compared to that in non-tumour tissues (P < 0.001). Moreover, GPX2 expression has statistically significant difference in the tumour histological grade of ESCC (P < 0.001), while there was no statistically significant difference in age, sex, tumour size, tumour location, gross morphology and clinical TNM stages (P > 0.05). Meanwhile, the expression of GPX2 protein was obviously down-regulated within poorly differentiated ESCC. Last, survival analysis revealed that tumour histological grade and clinical TNM stages, both of the clinical pathological parameters of ESCC, were associated with the prognosis of patients with ESCC (respectively, P = 0.009, HR (95 % CI) = 1.885 (1.212 ~ 2.932); P = 0.007, HR (95 % CI) = 2.046 (1.318 ~ 3.177)). More importantly, loss expression of GPX2 protein predicted poor prognosis in patients with ESCC (P < 0.001, HR (95 % CI) = 5.700 (2.337 ~ 13.907)).
Collectively, these results suggested that the expression of GPX2 was significantly up-regulated within ESCC tumour tissues. GPX2 might be an important predictor for the prognosis of ESCC and a potential target for intervention and treatment of ESCC.
潮汕地区位于中国南方广东省的沿海地区，食管鳞状细胞癌（ESCC）发病率较高。目前，ESCC的预后仍然很差，因此，迫切需要寻找有价值的分子生物标志物用于预后评估，以指导临床治疗。GPX2是一种硒蛋白，仅在胃肠道表达，在肿瘤发生过程中具有抗氧化损伤和抗肿瘤作用。
我们收集了161例ESCC患者样本，其中83例患者进行了随访。我们采用免疫化学分析、蛋白质印迹法和定量实时PCR检测ESCC样本中GPX2的表达。我们通过卡方检验或Fisher精确检验分析了161例ESCC患者的GPX2表达与临床病理参数之间的关系。采用Kaplan-Meier法和Cox回归评估ESCC组织中GPX2表达的生存分析。
与非肿瘤组织相比，肿瘤组织中检测到的GPX2表达水平显著更高（P < 0.001）。此外，GPX2表达在ESCC的肿瘤组织学分级上有统计学显著差异（P < 0.001），而在年龄、性别、肿瘤大小、肿瘤位置、大体形态和临床TNM分期上无统计学显著差异（P > 0.05）。同时，在低分化ESCC中，GPX2蛋白的表达明显下调。最后，生存分析显示，ESCC的临床病理参数肿瘤组织学分级和临床TNM分期均与ESCC患者的预后相关（分别为P = 0.009，HR（95%CI）= 1.885（1.2122.932）；P = 0.007，HR（95%CI）= 2.046（1.3183.177））。更重要的是，GPX2蛋白表达缺失预示着ESCC患者预后不良（P < 0.001，HR（95%CI）= 5.700（2.337~13.907））。
总体而言，这些结果表明ESCC肿瘤组织中GPX2的表达显著上调。GPX2可能是ESCC预后的重要预测指标，也是ESCC干预和治疗的潜在靶点。
